The long-term objective of this project is to develop an ultrasound contrast agent for detecting and characterizing vulnerable plaque. Vulnerable plaque is responsible for myocardial infarction and stroke. Early detection of vulnerable plaque would enable intervention to be performed before heart attack or stroke has occurred. In Phase I we expect to show feasibility in a mouse model and also to verify expression of the same epitopes in human specimens of vulnerable plaque. In Objective 1 microbubbles (MB) will be prepared targeted to epitopes present in vulnerable plaque: VCAM-1, dysregulated VWF multimers, P-selectin and LOX-1. MB will be testing using contrast enhanced ultrasound molecular imaging readout in a murine model of advanced inflammatory therosclerotic plaque. In Objective 2 we will test for presence of epitopes with antibodies to VCAM-1, GPIB-alpha, P-selectin and LOX-1 in the mice and also in human carotid endarterectomy specimens. We expect that one or more of the MB targeted to either VCAM-1, VWF, Pselectin or LOX-1 will enhance vulnerable plaque for detection by ultrasound and that the antibody studies will confirm expression of the same epitopes in both murine and human vulnerable plaque. In Phase II we will develop microbubbles specifically targeted to human epitopes.